| 1. |
- Bränn, Emma, et al.
(författare)
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Inflammatory markers in late pregnancy in association with postpartum depression-A nested case-control study.
- 2017
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 79, s. 146-159
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies indicate that the immune system adaptation during pregnancy could play a significant role in the pathophysiology of perinatal depression. The aim of this study was to investigate if inflammation markers in a late pregnancy plasma sample can predict the presence of depressive symptoms at eight weeks postpartum. Blood samples from 291 pregnant women (median and IQR for days to delivery, 13 and 7-23days respectively) comprising 63 individuals with postpartum depressive symptoms, as assessed by the Edinburgh postnatal depression scale (EPDS≥12) and/or the Mini International Neuropsychiatric Interview (M.I.N.I.) and 228 controls were analyzed with an inflammation protein panel using multiplex proximity extension assay technology, comprising of 92 inflammation-associated markers. A summary inflammation variable was also calculated. Logistic regression, LASSO and Elastic net analyses were implemented. Forty markers were lower in late pregnancy among women with depressive symptoms postpartum. The difference remained statistically significant for STAM-BP (or otherwise AMSH), AXIN-1, ADA, ST1A1 and IL-10, after Bonferroni correction. The summary inflammation variable was ranked as the second best variable, following personal history of depression, in predicting depressive symptoms postpartum. The protein-level findings for STAM-BP and ST1A1 were validated in relation to methylation status of loci in the respective genes in a different population, using openly available data. This explorative approach revealed differences in late pregnancy levels of inflammation markers between women presenting with depressive symptoms postpartum and controls, previously not described in the literature. Despite the fact that the results do not support the use of a single inflammation marker in late pregnancy for assessing risk of postpartum depression, the use of STAM-BP or the novel notion of a summary inflammation variable developed in this work might be used in combination with other biological markers in the future.
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| 2. |
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| 3. |
- Bengtsson, Jörgen, et al.
(författare)
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The use of a deuterated calibrator for in vivo recovery estimations in microdialysis studies
- 2008
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 97:8, s. 3433-3441
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Tidskriftsartikel (refereegranskat)abstract
- One of the crucial issues in quantitative microdialysis is the reliability of recovery estimates to correctly estimate unbound drug tissue concentrations. If a deuterated calibrator is used for retrodialysis, the calibrator has the same properties as the study drug. However, recovery of the calibrator may be affected by the presence of the drug in the tissues. The aim of this study was to investigate the recovery of deuterated morphine with time in the absence and presence of morphine in rat tissues. Microdialysis probes were placed in the brain and blood of eight rats. Ringer's solution containing D3-morphine was perfused throughout the study and recovery was estimated. After a stabilization period of 3 h, an exponential infusion of morphine was administered over 4 h. The presence of morphine did not affect the recovery of D3-morphine from brain or blood. The average recovery values (SD) were 0.145 (0.039) and 0.131 (0.048) during the stabilization and infusion periods, respectively, for the brain probe and 0.792 (0.055) and 0.790 (0.084), respectively, for the blood probe. The recovery of deuterated morphine was stable over time in the brain and in blood, and was not affected by the presence of pharmacologically concentrations of morphine.
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| 4. |
- Boström, Emma, et al.
(författare)
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Blood–Brain Barrier Transport Helps to Explain Discrepancies in In Vivo Potency between Oxycodone and Morphine
- 2008
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Ingår i: Anesthesiology. - 0003-3022 .- 1528-1175. ; 108:3, s. 495-505
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Tidskriftsartikel (refereegranskat)abstract
- Background The objective of this study was to evaluate the brain pharmacokinetic-pharmacodynamic relations of un-bound oxycodone and morphine to investigate the influence of blood-brain barrier transport on differences in potency between these drugs. Methods: Microdialysis was used to obtain unbound concentrations in brain and blood. The antinociceptive effect of each drug was assessed using the hot water tail-flick method. Population pharmacokinetic modeling was used to describe the bloodbrain barrier transport of morphine as the rate (Cl.) and extent (K-p,K-uu) of equilibration, where CLin is the influx clearance across the blood-brain barrier and Kp,,,, is the ratio of the unbound concentration in brain to that in blood at steady state. Results: The six-fold difference in K-p,K-uu between oxycodone and morphine implies that, for the same unbound concentration in blood, the concentrations of unbound oxycodone in brain will be six times higher than those of morphine. A joint pharmacokinetic-pharmacodynamic model of oxycodone and morphine based on unbound brain concentrations was developed and used as a statistical tool to evaluate differences in the pharmacodynamic parameters of the drugs. A power model using Effect = Baseline + Slope center dot C-gamma best described the data. Drug-specific slope and gamma parameters made the relative potency of the drugs concentration dependent. Conclusions: For centrally acting drugs such as opioids, pharmacokinetic-pharmacodynamic relations describing the interaction with the receptor are better obtained by correlating the effects to concentrations of unbound drug in the tissue of interest rather than to blood concentrations.
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| 5. |
- Boström, Emma, et al.
(författare)
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In Vivo Blood-Brain Barrier Transport of Oxycodone in the Rat : Indications for Active Influx and Implications for Pharmacokinetics/Pharmacodynamics
- 2006
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Ingår i: Drug Metabolism And Disposition. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0090-9556 .- 1521-009X. ; 34:9, s. 1624-1631
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Tidskriftsartikel (refereegranskat)abstract
- The blood-brain barrier (BBB) transport of oxycodone was studied in rats. Microdialysis probes were inserted into the striatum and vena jugularis. Ten animals were given a bolus dose followed by a 120-min constant rate infusion to study the steady-state concepts of oxycodone BBB equilibration. Another 10 animals were given a 60-min constant rate infusion to study the rate of equilibration across the BBB. Oxycodone-D3 was used as a calibrator for the microdialysis experiments. The samples were analyzed with a liquid chromatography-tandem mass spectrometry method and a population pharmacokinetic model was used to simultaneously fit all the data using NONMEM. A two-compartment model which allowed for a delay between the venous and arterial compartments best described the pharmacokinetics for oxycodone in blood and plasma, whereas a one-compartment model was sufficient to describe the pharmacokinetics in the brain. The BBB transport of oxycodone was parameterized as CL(in) and K(p,uu). CL(in) describes the clearance of oxycodone across the BBB into the brain, whereas K(p,uu) describes the extent of drug equilibration across the BBB. CL(in) across the BBB was estimated to 1910 microl/min x g brain. K(p,uu) was estimated to 3.0, meaning that the unbound concentration of oxycodone in brain was 3 times higher than in blood, which is an indication of active influx of oxycodone at the BBB. This is the first evidence of an opioid having an unbound steady-state concentration in brain that is higher than unity, which can explain potency discrepancies between oxycodone and other opioids.
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| 6. |
- Boström, Emma, et al.
(författare)
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Oxycodone Pharmacokinetics and Pharmacodynamics in the Rat in the Presence of the P-Glycoprotein Inhibitor PSC833
- 2005
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 94:5, s. 1060-1066
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to investigate the in vivo influence of the P-glycoprotein (P-gp) inhibitor PSC833 on the plasma pharmacokinetics, total brain concentrations and tail-flick latency of oxycodone in rats. Eight rats each received an infusion of PSC833 or vehicle without PSC833. One hour later, all animals received 0.3 mg/kg oxycodone as a 1-h infusion. Plasma samples were taken, and tail-flick latency was monitored during the infusion and for 2 h thereafter. The brains were collected at the end of the experiment. There were no differences between the two groups in area under the plasma oxycodone concentration-time curve from time zero to infinity, or oxycodone plasma clearance, volume of distribution at steady-state, or half-life. There were no differences in average total brain oxycodone concentrations at 180 min, nor were there any differences in average tail-flick latency for the PSC833 and control groups. In conclusion, coadministration of PSC833 did not alter the plasma pharmacokinetics, brain concentrations, or associated tail-flick latency of oxycodone, indicating that oxycodone is not a P-gp substrate in the rat. This has important clinical implications, as it indicates that oxycodone, unlike some other opioids, will not interact at the blood-brain barrier (BBB) with concomitantly administered P-gp substrates.
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| 7. |
- Boström, Emma, 1975-
(författare)
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Pharmacokinetics and Pharmacodynamics of Oxycodone and Morphine with Emphasis on Blood-Brain Barrier Transport
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The pharmacokinetics and pharmacodynamics of oxycodone and morphine was investigated and related to the transport across the blood-brain barrier (BBB) in rats. The influence of a P-glycoprotein (P-gp) inhibitor on the plasma pharmacokinetics and pharmacodynamics of oxycodone was evaluated. Microdialysis experiments were conducted to evaluate the unbound pharmacokinetics, including the rate and extent of transport across the BBB, of oxycodone and morphine. Mathematical models were used to assess the pharmacokinetics and also the relationship between pharmacokinetics and pharmacodynamics of the drugs.Oxycodone clearance, volume of distribution at steady-state, half-life, total brain tissue concentrations and tail-flick latency were all unaffected when a P-gp inhibitor was co-administered with oxycodone as compared to a control group. The lack of differences between the groups indicates that oxycodone BBB transport is not affected by P-gp inhibition. Investigating the unbound concentrations of oxycodone in brain and blood using microdialysis revealed an exciting finding. At steady-state, the unbound concentration in brain was 3 times higher than in blood (i.e. a Kp,uu of 3), indicating that active influx is involved in the BBB transport of oxycodone. In contrast, the Kp,uu of morphine was estimated to 0.56, which is an indication that active efflux mechanisms are involved in the BBB transport of morphine. This means that based on the same unbound concentration in blood, an approximately 6-fold higher unbound concentration of oxycodone compared to morphine will be reached in the brain. Using pharmacokinetic-pharmacodynamic modelling, the unbound brain concentrations of oxycodone and morphine were correlated to the tail-flick latency in vivo. The relative potency of the drugs was found to be concentration dependent with an infliction point of 55 nM.In summary, this thesis emphasise the importance of taking the local brain pharmacokinetics into consideration when investigating the pharmacokinetics and the pharmacokinetic-pharmacodynamic relationships of centrally acting drugs.
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| 8. |
- Boström, Emma, et al.
(författare)
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The Use of Liquid Chromatography/Mass Spectrometry for Quantitative Analysis of Oxycodone, Oxymorphone and Noroxycodone in Ringer Solution, Rat Plasma and Rat Brain Tissue
- 2004
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Ingår i: Rapid Communications in Mass Spectrometry. - : Wiley. - 0951-4198 .- 1097-0231. ; 18:21, s. 2565-2576
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Tidskriftsartikel (refereegranskat)abstract
- Sensitive and reproducible methods for the determination of oxycodone, oxymorphone and noroxycodone in Ringer solution, rat plasma and rat brain tissue by liquid chromatography/mass spectrometry are described. Deuterated analogs of the substances were used as internal standards. Samples in Ringer solution were analyzed by direct injection of 10 microL Ringer solution diluted by an equal volume of water. The limit of quantification was 0.5 ng/mL and the method was linear in the range of 0.5-150 ng/mL for all substances. To analyze oxycodone and oxymorphone in rat plasma, 50 microL of plasma were precipitated with acetonitrile, and the supernatant was directly injected onto the column. To analyze oxycodone, oxymorphone and noroxycodone in rat plasma, 100 microL of rat plasma were subjected to a C18 solid-phase extraction (SPE) procedure, before reconstituting in mobile phase and injection onto the column. For both methods the limit of quantification in rat plasma was 0.5 ng/mL and the methods were linear in the range of 0.5-250 ng/mL for all substances. To analyze the content of oxycodone, oxymorphone and noroxycodone in rat brain tissue, 100 microL of the brain homogenate supernatant were subjected to a C18 SPE procedure. The limit of quantification of oxycodone was 20 ng/g brain, and for oxymorphone and noroxycodone 4 ng/g brain, and the method was linear in the range of 20-1000 ng/g brain for oxycodone and 4-1000 ng/g brain for oxymorphone and noroxycodone. All methods utilized a mobile phase of 5 mM ammonium acetate in 45% acetonitrile, and a SB-CN column was used for separation. The total run time of all methods was 9 min. The intra-day precision and accuracy were <11.3% and <+/-14.9%, respectively, and the inter-day precision and accuracy were <14.9% and <+/-6.5%, respectively, for all the concentrations and matrices described.
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| 9. |
- Boström, Johan, et al.
(författare)
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Comparative cell cycle transcriptomics reveals synchronization of developmental transcription factor networks in cancer cells
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- The cell cycle coordinates core functions such as replication and cell division. However, cell-cycle-regulated transcription in the control of non-core functions, such as cell identity maintenance through specific transcription factors (TFs) and signalling pathways remains unclear. Here, we provide a resource consisting of mapped transcriptomes in unsynchro-nized HeLa and U2OS cancer cells sorted for cell cycle phase by Fucci reporter expression. We developed a novel algorithm for data analysis that enables efficient visualization and data comparisons and identified cell cycle synchronization of Notch signalling and TFs associated with development. Furthermore, the cell cycle synchronizes with the circadian clock, providing a possible link between developmental transcriptional networks and the cell cycle. In conclusion we find that cell cycle synchronized transcriptional patterns are temporally compartmentalized and more complex than previously anticipated, involving genes, which control cell identity and development.
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| 10. |
- Boström, Tove, et al.
(författare)
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Investigating the correlation of protein and mRNA levels in human cell lines using quantitative proteomics and transcriptomics
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- An important topic of discussion in proteomics is the degree of correlation of RNA and protein levels in cells, tissues and organs. In this study, the difference in protein and mRNA levels for a number of selected gene targets were investigated across six human cell lines using quantitative proteomics and next generation sequencing-based transcriptomics. The copy numbers of 32 proteins were determined using an absolute quantitative proteomics approach (PrEST-SILAC), where heavy isotope-labeled protein fragments were used as internal standards. A cross evaluation of protein copy numbers determined by mass spectrometry and staining profiles using immunohistochemistry showed good correlation. The mRNA levels were determined using RNA sequencing based on digital counting of sequencing reads and the levels determined as FPKM values. Comparison of the relative variations in mRNA and protein levels for individual genes across the six cell lines showed correlation between protein and mRNA levels, including six genes with high variability in expression levels in the six cell lines resulting in an average correlation of 0.9 (Spearman's rank coefficient). In summary, the analysis of the selected protein targets supports the conclusion that the translation rate across cell lines correlates for a particular gene, suggesting that individual protein levels can be predicted from the respective mRNA levels by defining the relation between protein and mRNA, specific for each human gene.
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| 11. |
- Edfors, Fredrik, et al.
(författare)
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Immunoproteomics using polyclonal antibodies and stable isotope-labeled affinity-purified recombinant proteins
- 2014
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 13:6, s. 1611-1624
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Tidskriftsartikel (refereegranskat)abstract
- AThe combination of immuno-based methods and mass spectrometry detection has great potential in the field of quantitative proteomics. Here, we describe a new method (immuno-SILAC) for the absolute quantification of proteins in complex samples based on polyclonal antibodies and stable isotope-labeled recombinant protein fragments to allow affinity enrichment prior to mass spectrometry analysis and accurate quantification. We took advantage of the antibody resources publicly available from the Human Protein Atlas project covering more than 80% of all human protein-coding genes. Epitope mapping revealed that a majority of the polyclonal antibodies recognized multiple linear epitopes, and based on these results, a semi-automated method was developed for peptide enrichment using polyclonal antibodies immobilized on protein A-coated magnetic beads. A protocol based on the simultaneous multiplex capture of more than 40 protein targets showed that approximately half of the antibodies enriched at least one functional peptide detected in the subsequent mass spectrometry analysis. The approach was further developed to also generate quantitative data via the addition of heavy isotope-labeled recombinant protein fragment standards prior to trypsin digestion. Here, we show that we were able to use small amounts of antibodies (50 ng per target) in this manner for efficient multiplex analysis of quantitative levels of proteins in a human HeLa cell lysate. The results suggest that polyclonal antibodies generated via immunization of recombinant protein fragments could be used for the enrichment of target peptides to allow for rapid mass spectrometry analysis taking advantage of a substantial reduction in sample complexity. The possibility of building up a proteome-wide resource for immuno-SILAC assays based on publicly available antibody resources is discussed.
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| 12. |
- Edvinsson, Åsa, 1982-, et al.
(författare)
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Lower inflammatory markers in women with antenatal depression brings the M1/M2 balance into focus from a new direction
- 2017
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Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 80, s. 15-25
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Tidskriftsartikel (refereegranskat)abstract
- Background: Antenatal depression and use of serotonin reuptake inhibitors (SSRI) in pregnancy have both been associated with an increased risk of poor pregnancy outcomes, such as preterm birth and impaired fetal growth. While the underlying biological pathways for these complications are poorly understood, it has been hypothesized that inflammation may be a common physiological pathway. The aim of the present study was to assess peripheral inflammatory markers in healthy women, women with antenatal depression, and in women using SSRI during pregnancy.Methods: 160 healthy pregnant controls, 59 women with antenatal depression and 39 women on treatment with SSRIs were included. The relative levels of 92 inflammatory proteins were analyzed by proximity extension assay technology.Results: Overall, 23 of the inflammatory markers were significantly lower in women with antenatal depression and in women on treatment with SSRIs in comparison with the healthy controls. No difference in any of the inflammatory markers was observed between women with antenatal depression and those who were using SSRI. Top three inflammatory markers that were down-regulated in women with antenatal depression were TNF-related apoptosis-inducing ligand (TRAIL), p = 0.000001, macrophage colony-stimulating factor 1 (CSF-1), p = 0.000004, and fractalkine (CX3CL1), p =0.000005. Corresponding inflammatory markers in SSRI users were CSF-1, p = 0.000011, vascular endothelial growth factor A (VEGF-A), p =0.000016, and IL-15 receptor subunit alpha (IL-15RA), p = 0.000027. The inflammatory markers were negatively correlated with cortisone serum concentrations in controls, but not in the cases. Differential DNA methylation of was found for seven of these inflammatory markers in an independent epigenetics cohort.Conclusion: Women with antenatal depression or on SSRI treatment have lower levels of a number of peripheral inflammatory markers than healthy pregnant controls. Hypothetically, this could be due to dysregulated switch to the pro-M2 milieu that characterizes normal third trimester pregnancy. However, longitudinal blood sampling is needed to elucidate whether the presumably dysregulated M2 shift is driving the development of antenatal depression or is a result of the depression.
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| 13. |
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| 14. |
- Espefält Westin, Ulrika, et al.
(författare)
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Direct nose-to-brain transfer of morphine after nasal administration to rats
- 2006
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 23:3, s. 565-572
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of this study was to quantify the olfactory transfer of morphine to the brain hemispheres by comparing brain tissue and plasma morphine levels after nasal administration with those after intravenous administration. METHODS: Morphine (1.0 mg/kg body weight) was administered via the right nostril or intravenously as a 15-min constant-rate infusion to male rats. The content of morphine and its metabolite morphine-3-glucuronide in samples of the olfactory bulbs, brain hemispheres, and plasma was assessed using high-performance liquid chromatography, and the areas under the concentration-time curves (AUC) were calculated. RESULTS: At both 5 and 15 min after administration, brain hemisphere morphine concentrations after nasal administration were similar to those after i.v. administration of the same dose, despite lower plasma concentrations after nasal administration. The brain hemispheres/plasma morphine AUC ratios for the 0-5 min period were thus approximately 3 and 0.1 after nasal and i.v. administration, respectively, demonstrating a statistically significant early distribution advantage of morphine to the brain hemispheres via the nasal route. CONCLUSION: Morphine is transferred via olfactory pathways to the brain hemispheres, and drug transfer via this route significantly contributes to the early high brain concentrations after nasal administration to rats.
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| 15. |
- Hjerpe, Karin, et al.
(författare)
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Utsläpp av växthusgaser från torvmark
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Dikad torvmark i Sverige avgav sammanlagt drygt 11,4 miljoner ton koldioxidekvivalenter år 2012, enligt den senaste klimatrapporteringen. Denna mängd kan jämföras med de totala svenska utsläppen av växthusgaser, som beräknades uppgå till 57,6 miljoner ton koldioxidekvivalenter samma år. En åtgärd som skulle kunna minska utsläppen av växthusgaser från dikad torvmark är att återställa marken till våtmark, vilket minskar avgången av koldioxid och lustgas från marken. Samtidigt ökar avgången av metan, men minskningen av koldioxid- och lustgasutsläppen är större, vilket innebär att utsläppen av växthusgaser från marken totalt sett minskar. Om de ekonomiska resurserna för att återställa dikad torvmark till våtmark är begränsade bör man i första hand återställa dikade torvmarker som är stora källor för växthusgaser till våtmark. Studier av växthusgasutsläpp från dikade torvmarker som används för skogsproduktion visar att näringsrika och väldränerade marker är större källor för växthusgaser än näringsfattigare, fuktigare marker. Vi bedömer därför att det ur ett klimatperspektiv är viktigast att återställa dikad skogsmark med en kol:kväve-kvot under 25 som är frisk-fuktig eller torrare. Dikad torvmark som används för naturbete avger mindre växthusgaser än åkermark på dikad torvmark och därför är det viktigare att återställa åkermark till våtmark. Avgången av växthusgaser varierar mycket mellan olika åkrar på dikad torvmark. Det är dock inte möjligt att identifiera åkrar på dikad torvmark som är stora källor för växthusgaser utifrån markfuktighet eller kol:kväve-kvot, och inte heller utifrån några andra faktorer som är enkla att mäta. Detta beror sannolikt på att åkermarken generellt är så pass väldränerad och näringsrik att varken syreeller kvävetillgången är begränsande för avgången av koldioxid och lustgas. I ett längre tidsperspektiv kommer dikad torvmark att avge koldioxid och lustgas så länge det finns ett syresatt torvlager. Därför bedömer vi att det är viktigast att återställa dikad åkermark med tjockt torvlager till våtmark. Därtill bör mark som inte längre aktivt brukas prioriteras framför mark som fortfarande är i bruk. Utsläppen av växthusgaser verkar inte automatiskt minska när brukandet upphör och även om marken sannolikt kommer att försumpas på sikt, vilket innebär att utsläppen av växthusgaser minskar, kan det ta väldigt lång tid. Dessutom borde kostnaderna för att återställa marken till våtmark i genomsnitt bli lägre om marken inte längre används. Hur mycket avgången av växthusgaser minskar när dikad torvmark återställs till våtmark beror inte bara på hur stor avgången av växthusgaser från den dikade marken var utan också på hur stor avgången från den anlagda våtmarken blir. Utsläppen från våtmarken påverkas av hur den anläggs och sköts. För att våtmarken ska avge så lite växthusgaser som möjligt bör grundvattennivån höjas så mycket att förhållandena före dikningen återskapas. Om våtmarken anläggs på mark som använts för jordbruksproduktion bör dessutom vegetationen tas bort före återställandet. Anläggning av våtmarker kan också ge andra nyttor – våtmarkerna kan bland annat gynna biologisk mångfald och minska näringsläckaget till våra sjöar och vattendrag. När en våtmark ska anläggas och skötas behöver man ta hänsyn till alla dessa aspekter så att våtmarken ger så stor nytta som möjligt.
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| 16. |
- Krantz, Mattias, et al.
(författare)
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Parental experiences of having a child with CLN3 disease (juvenile Batten disease) and how these experiences relate to family resilience
- 2022
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Ingår i: Child: Care, Health and Development. - : Wiley. - 0305-1862 .- 1365-2214. ; 48:5, s. 842-851
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Tidskriftsartikel (refereegranskat)abstract
- Background: CLN3 disease is a neurodegenerative condition presenting in the first decade of life typically leading to death in the third decade. The earliest symptom is rapidly progressive visual impairment followed by intellectual and motor impairments, epilepsy and behavioural disturbances. There are limited data on how the condition affects the family system or the role of family resilience in paediatric neurodegenerative diseases. Methods: Semi-structured interviews were conducted with eight parents (five mothers and three fathers) of five children with CLN3. Interview questions focused on the experience of having a child with CLN3, its impact on the family system as well as the concept of family resilience. Data were analysed via thematic analysis. Results: The thematic analysis resulted in four main themes. The theme ‘recurring losses’ included the feeling of losing a healthy child, the child's loss of abilities and loss of relationships. The theme ‘disruption to the family system’ included that siblings could be ‘side-lined’, the potential negative impact on romantic relationships and difficulties finding time to oneself. The theme ‘Society is not developed for a progressive disease’ highlighted the difficulties parents faced with respect to contacts with the health and/or social insurance system. The paediatric health care system was seen as supportive, but the adult health care system was not seen as fit for the purpose. Regarding family resilience, parents felt that the disease forced them to reconsider what was important in life. Several parents described that they learned to value small moments of joy and create deep connections through involvement in family routines and rituals. Conclusions: CLN3 places a very significant burden on the family system including parental feelings of loss, impact on family relationships and lack of understanding within the health/social insurance systems. The concept of family resilience may be useful in understanding the experiences of families affected by paediatric neurodegenerative conditions.
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| 17. |
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| 18. |
- Olofsson, Sven-Olof, 1947, et al.
(författare)
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The formation of lipid droplets: possible role in the development of insulin resistance/type 2 diabetes.
- 2011
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Ingår i: Prostaglandins, leukotrienes, and essential fatty acids. - : Elsevier BV. - 1532-2823 .- 0952-3278. ; 85:5, s. 215-8
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Tidskriftsartikel (refereegranskat)abstract
- Neutral lipids are stored in so-called lipid droplets, which are formed as small primordial droplets at microsomal membranes and increase in size by a fusion process. The fusion is catalyzed by the SNARE proteins SNAP23, syntaxin-5 and VAMP4. SNAP23 is involved in the insulin dependent translocation of GLUT4 to the plasma membrane, and has an important role in the development of insulin resistance. Thus fatty acids relocalize SNAP23 from the plasma membrane (and the translocation of GLUT 4) to the interior of the cell giving rise to insulin resistance. Moreover this relocalization is seen in skeletal muscles biopsies from patients with type 2 diabetes compared to matched control. Thus a missorting of SNAP23 is essential for the development of insulin resistance.
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| 19. |
- Sadiq, Muhammad Waqas, 1981-, et al.
(författare)
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Oxymorphone active uptake at the blood-brain barrier and population modeling of its pharmacokinetic-pharmacodynamic relationship
- 2013
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Ingår i: Journal of Pharmaceutical Sciences. - Wiley : Elsevier BV. - 0022-3549 .- 1520-6017. ; 102:9, s. 3320-3331
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to characterize the blood–brain barrier (BBB) transport and pharmacokinetics–pharmacodynamics (PKPD) relationship of oxymorphone and to further elucidate its possible contribution to oxycodone analgesia. The BBB transport of oxymorphone was studied using microdialysis in male Sprague–Dawley rats. Samples from microdialysis blood and brain probes, brain tissue, and plasma were analyzed by liquid chromatography with tandem mass spectrometry. The effect was measured as tail-flick latency. The study consisted of a PKPD experiment with combined microdialysis and antinociceptive measurements (n = 8), and another antinociceptive effect experiment (n = 9) using a 10 times lower dose. The combined data were analyzed with an integrated PKPD model in nonlinear mixed effect modeling utilizing a specific method (M3) for handling missing PD observations. The concentration of unbound oxymorphone was higher in brain than in blood, with a ratio of 1.9 (RSE, 9.7%), indicating active uptake at the BBB. The integrated PKPD model described the oxymorphone BBB transport and PKPD relationship successfully, with an EC50 in the brain of 63 ng/mL, and the M3 method was able to address the issue of censored observations. Oxymorphone has active uptake transport at the BBB in rats, with moderate uptake clearance to the brain. Its contribution to analgesia after oxycodone administration is not significant.
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| 20. |
- Weick, Linn, 1991, et al.
(författare)
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Patient experience of implant loss after immediate breast reconstruction : An interpretative phenomenological analysis
- 2023
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Ingår i: Health Care for Women International. - : Taylor & Francis Group. - 0739-9332 .- 1096-4665. ; 44:1, s. 61-79
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Tidskriftsartikel (refereegranskat)abstract
- Immediate breast reconstruction (IBR) is an integral part of modern breast cancer treatment. Our aim was to investigate patient experience with implant loss after IBR by using interpretative phenomenological analysis (IPA). We conducted semi-structured interviews with eight informants. We analyzed data according to the IPA flexible seven-stage process and four main themes were developed: immediate breast reconstruction as the indisputable choice, a difficult experience, an altered body: redefining normality, and trying to cope. The experience of implant loss appears to affect women for many years and might overshadow some of the benefits of IBR.
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